Description:
<jats:sec><jats:label /><jats:p>Injury of cerebral blood vessels (CBV) and neurons in Alzheimer's disease (AD) partially results from nitric oxide (NO) overproduction in microglia and astrocytes. Formation of NO stores protects CBV against NO toxicity by binding excessive NO. We have shown that prior adaptation to intermittent hypoxia (AH; simulated altitude 4,000 m; 4 h daily, 14 days) reduced memory loss and neurodegeneration in rats with experimental AD (EAD), and we proposed that enhancing protective mechanisms against NO overproduction might contribute to the beneficial effect of AH. Here EAD was modeled in rats by a bilateral injection of beta‐amyloid peptide (Ab) fragment (25‐35) into <jats:italic>n. basalis magnocellularis</jats:italic>. NO production was assessed in brain tissue by measuring NO<jats:sub>2</jats:sub>+NO<jats:sub>3</jats:sub>. NO stores were detected by increases in Doppler‐measured cerebral blood flow (CBF) in response to N‐acetylcysteine (NAC) which releases NO from NO stores. Ab significantly increased NO production in rat brain (25±2.0 vs 40±3.3 μmol/g tissue, respectively). AH prevented NO overproduction in Ab‐treated rats (19±1.6 μmol/g tissue). In rats with EAD, NAC increased CBF by 18.4±6.2%, which reflected formation of NO stores; NO stores were absent in CBV from control rats. Size of NO stores in adapted rats with EAD was significantly larger (31±3.5%) than in nonadapted rats with EAD. Thus, AH protection against Ab‐induced NO overproduction involves two mechanisms: restricting excessive NO synthesis and expanding NO‐storing capacity of CBV. (<jats:italic>Supported by RFBR grant 07‐04‐00650</jats:italic>)</jats:p></jats:sec>